This research proposal involves the long term development and application of artificial support system that could be used in the treatment of acute reversible hepatic failure and in conjunction with hepatic transplantation. Animal models of acute liver failure will be investigated so as to develop a tool for attempts to (1) gain insights into the biochemical nature of the metabolic coma, and (2) evaluate critically, and in a controlled manner, various therapeutic endeavors. Acetaminophen induced hepatic necrosis in the rat was found to be too unpredictable and, therefore, the yellow phosphorus model of liver failure in the dog will be evaluated. Support systems such as hemodialysis, resin hemoperfusion, and coated charcoal hemoperfusion will be tested for their effect on coma and survival under experimental conditions. If such devices or combinations thereof can be found to be strikingly beneficial to animal models in acute liver failure, then a controlled trial in human would be indicated.